Endothelial monocyte-activating polypeptide-II (EMAP-II): a novel inducer of lymphocyte apoptosis.

Abstract

The novel, proinflammatory cytokine endothelial monocyte-activating polypeptide-II (EMAP-II) was first found in tumor cell supernatants. EMAP-II is closely related or identical to the p43 auxiliary protein of the multisynthase complex, which is involved in protein synthesis. In vitro, EMAP-II induces procoagulant activity, increased expression of E- and P-selectins and tumor necrosis factor receptor-1, and ultimately, programmed cell death (apoptosis) in cultured endothelial cells. EMAP-II is also chemotactic for monocytes and neutrophils. However, the role of the p43/EMAP-II cytokine form in tumors is not understood. We hypothesized an immune-regulatory role within neoplastic tissues and investigated its effects on lymphocytes. EMAP-II causes a dose-dependent inhibition of proliferation and apoptosis in Jurkat T cells and mitogen-activated peripheral blood mononuclear cells. Coculture with DLD-1 colorectal cancer cells or media conditioned by these cells induces apoptosis in Jurkat cells, which is partially reversed by antibodies against EMAP-II. Our data suggest that EMAP-II constitutes a component of a novel, immunosuppressive pathway in solid tumors, which is not normally expressed outside the cell but in tumors, may be subject to abnormal processing and released from tumor cells.

• Authors: J C Murray, Y M Heng, P Symonds, K Rice, W Ward, M Huggins, I Todd, R A Robins
• Journal: Journal of leukocyte biology (J Leukoc Biol) Vol. 75 Issue 5 Pg. 772-6 (May 2004) ISSN: 0741-5400 [Print] England
• PMID: 14982944 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Cytokines
• Neoplasm Proteins
• RNA-Binding Proteins
• small inducible cytokine subfamily E, member 1

Topics

• Adjuvants, Immunologic (pharmacology, physiology)
• Apoptosis (drug effects)
• Cell Division (drug effects)
• Cell Line, Tumor
• Coculture Techniques
• Colorectal Neoplasms (pathology)
• Cytokines (pharmacology, physiology)
• Humans
• Leukocytes, Mononuclear (cytology, drug effects)
• Lymphocyte Activation
• Lymphocytes (cytology)
• Neoplasm Proteins (pharmacology, physiology)
• RNA-Binding Proteins (pharmacology, physiology)
• T-Lymphocytes (cytology, drug effects)